epothilone d as second-line treatment for patients with advanced or metastatic refractory colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: drugs used in chemotherapy such as epothilone d work in different ways to stop tumor cells from dividing so they stop growing or die. purpose: this phase ii trial is studying how well epothilone d works as second-line therapy in treating patients with advanced or metastatic refractory colorectal cancer.

objectives: primary * determine the antitumor activity of epothilone d as second-line treatment, in terms of objective response rate, in patients with advanced or metastatic refractory colorectal cancer. secondary * determine the safety of this drug in these patients. * determine the response duration in patients responding to treatment with this drug. * determine time to tumor progression and overall survival in patients treated with this drug. * correlate efficacy and safety with plasma concentrations of this drug and its major metabolites in these patients. outline: this is an open-label, multicenter study. patients receive epothilone d iv over 90 minutes on days 1, 8, and 15. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. patients are followed every 3 months. projected accrual: a total of 19-69 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed advanced or metastatic adenocarcinoma of the colon or rectum * evidence of at least 1 site of unidimensionally measurable disease by radiography or physical examination * failed 1 prior treatment with a fluoropyrimidine in combination with either irinotecan or oxaliplatin for advanced or metastatic disease * no known cns metastases patient characteristics: age * 18 and over performance status * ecog 0-1 life expectancy * not specified hematopoietic * hemoglobin ≥ 9 g/dl * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 hepatic * bilirubin ≤ 1.5 times upper limit of normal (uln) * ast and alt ≤ 2.5 times uln (5 times uln if hepatic metastases are present) * alkaline phosphatase ≤ 5 times uln renal * creatinine ≤ 1.5 times uln cardiovascular * no new york heart association class iii or iv congestive heart failure * no qtc \> 450 msec for males or \> 470 msec for females * no personal or family history of congenital long qt syndrome other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective barrier contraception * no pre-existing neuropathy grade 2 or greater * no documented grade 3 or 4 hypersensitivity reaction to prior therapy containing cremophor * no infection requiring parenteral or oral anti-infective treatment * no altered mental status or psychiatric condition that would preclude giving informed consent * no other medical condition that would preclude study participation * no other malignancy within the past 5 years except cured basal cell skin cancer, carcinoma in situ of the cervix or bladder, or stage t1 or t2 prostate cancer with a prostate-specific antigen \< 2 ng/ml prior concurrent therapy: biologic therapy * no concurrent sargramostim (gm-csf) * no concurrent routine prophylactic use of filgrastim (g-csf) chemotherapy * see disease characteristics * at least 3 weeks since prior chemotherapy and recovered endocrine therapy * not specified radiotherapy * at least 3 weeks since prior radiotherapy and recovered surgery * at least 3 weeks since prior surgery and recovered other * more than 3 weeks since prior investigational agents (therapeutic or diagnostic) * no other concurrent therapy for advanced or metastatic colorectal cancer * no other concurrent investigational drugs

Keywords: recurrent colon cancer recurrent rectal cancer stage iii colon cancer stage iii rectal cancer stage iv colon cancer stage iv rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum